Diabetes is characterized by chronic high blood glucose levels. There were about 250 million diabetes patients all around the world as of 2007, especially in undeveloped and developing countries. It is estimated that there will be 380 million patients by 2025. Therefore, diabetes is a critical global problem.
Insulin is delivered in liquid injection form for diabetes treatment because of its short half-life and degradation in the gastrointestinal track. It must be given to the patients frequently, which brings great inconvenience and economic burden. There is a great demand for the development of a more convenient non-injection form for insulin. An oral dosage form has been widely studied. Insulin pH-sensitive nanoparticles can control insulin release and improve its oral bioavailability.
PCT publication WO2010113177-A2 discloses an oral insulin pH-sensitive agent comprising insulin and Eudragit L100. The agent shows a good pH-sensitive property when the particle size is 40 μm; however this size is not suitable for insulin absorption. Further, the disclosed preparation technique has some limitations since the required double emulsion of an agent comprising liquid paraffin is unstable and the evaporation of the solvent is slow.
Patent application publication US2010021549-A1 provides a core-shell particle comprising insulin and pH-sensitive polymers. The pH-sensitive polymers are HPMCP and HPMCAS. The release of insulin from the particle is slow in an acidic medium while fast in a neutral medium. The particle is prepared by a fluidized bed spraying technique with 2 mm particle size.
Paper (J Pharm Sci-US, 2007, 96, 421) describes an oral insulin pH-sensitive nanoparticle composed of HP55 and PLGA. The nanoparticles are prepared by a solvent evaporation method. In this method, both polymers and insulin are dissolved into a solvent containing water, which has some limitations. Although phase separation is easily generated when the concentration is high, the process suffers from low encapsulation efficiency. Further, although insulin easily diffuses outwards, a lower pH-sensitive property is a result.
HP55 is a pH-sensitive cellulose coating designed for use in enteric coating materials. HP55 can withstand prolonged contact with an acidic gastric environment, but readily dissolves in the mildly acidic to neutral fluid of the small intestine. HP55, when used to prepare insulin-loaded nanoparticles, is able to reduce insulin release in the stomach and thus increase the bioavailability.
However, there is still a need for orally-deliverable insulin particles having increased bioavailability and a need for processes that produce a high yield of such insulin particles.